Intradermal photosensitisation facilitates stimulation of MHC class-I restricted CD8 T-cell responses of co-administered antigen
| Autor: | Anders Høgset, Thomas M. Kündig, Ying Waeckerle-Men, Pål Johansen, Pål Kristian Selbo, Monika Håkerud |
|---|---|
| Přispěvatelé: | University of Zurich, Johansen, Pål |
| Rok vydání: | 2014 |
| Předmět: |
Porphyrins
Injections Intradermal Light Ovalbumin medicine.medical_treatment Antigen presentation 3003 Pharmaceutical Science Melanoma Experimental Genes MHC Class I Pharmaceutical Science 610 Medicine & health Mice Transgenic Stimulation CD8-Positive T-Lymphocytes Major histocompatibility complex Cell Line Mice Cytosol Antigen Cancer immunotherapy Cell Line Tumor MHC class I medicine Animals Cytotoxic T cell Antigens Photosensitizing Agents biology 10177 Dermatology Clinic DNA-Binding Proteins Mice Inbred C57BL Immunology biology.protein Female Immunization CD8 |
| Zdroj: | Journal of Controlled Release. 174:143-150 |
| ISSN: | 0168-3659 |
| Popis: | The protection or treatment of several immunological disorders is dependent on the antigen-specific and cytotoxic CD8 T cells. However, vaccines aimed at stimulating CD8 T-cell responses are typically ineffective because vaccine antigens are primarily processed by the MHC class-II and not the MHC class-I pathway of antigen presentation: the latter requires cytosolic delivery of antigen. In order to facilitate targeting of antigen to cytosol, the antigen was combined with the photosensitiser TPCS2a (disulfonated tetraphenyl chlorin) and administered intradermally to mice. The photosensitiser was activated by illumination of the injection site. This photochemical internalization (PCI) strongly increased the stimulation of CD8 T-cell responses as measured by antigen-specific proliferation and secretion of pro-inflammatory cytokines. Fluorescence microscopy showed that delivery to cytosol was TPCS2a dependent and occurred by light-induced disruption of TPCS2a- and antigen-containing endosomes. PCI-based vaccination prevented growth of malignant B16 cells as compared with vaccination without PCI. In conclusion, PCI represents a potent tool for delivery of antigens to cytosol for stimulation of cytotoxic CD8 T-cell responses. This study demonstrated a first proof-of-principle for PCI-mediated immunisation with potential application in cancer immunotherapy. |
| Databáze: | OpenAIRE |
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